GM1 gangliosidosis type II: Results of a 10-year prospective study.

PURPOSE: GM1 gangliosidosis (GM1) a lysosomal disorder caused by pathogenic variants in GLB1, is characterized by relentless neurodegeneration. There are no approved treatments. METHODS: Forty-one individuals with type II (late-infantile and juvenile) GM1 participated in a single-site prospective observational study. RESULTS: Classification of 37 distinct variants using American College of Medical Genetics and Genomics criteria resulted in the upgrade of 6 and the submission of 4 new variants. In contrast to type I infantile disease, children with type II had normal or near normal hearing and did not have cherry-red maculae or hepatosplenomegaly. Some older children with juvenile onset disease developed thickened aortic and/or mitral valves. Serial magnetic resonance images demonstrated progressive brain atrophy, more pronounced in late infantile patients. Magnetic resonance spectroscopy showed worsening elevation of myo-inositol and deficit of N-acetyl aspartate that were strongly correlated with scores on the Vineland Adaptive Behavior Scale, progressing more rapidly in late infantile compared with juvenile onset disease. CONCLUSION: Serial phenotyping of type II GM1 patients expands the understanding of disease progression and clarifies common misconceptions about type II patients; these are pivotal steps toward more timely diagnosis and better supportive care. The data amassed through this 10-year effort will serve as a robust comparator for ongoing and future therapeutic trials.

Genetic aortopathies: a case-based approach to multidisciplinary program development.

PURPOSE OF REVIEW: The incorporation of genetic counseling and testing is essential to evaluation and management of thoracic aortic disease in patients under 60 years of age and those with family histories suspicious for heritable thoracic aortic disease and disorders associated with increased risk for acute type-A aortic dissection. RECENT FINDINGS: As many as 20% of individuals with thoracic aortic disease under the age of 60 years have autosomal dominant patterns of inheritance. A considerable number of heritability factors remain undefined for these families. SUMMARY: Genetic aortopathy programs require a collaborative approach including cardiovascular specialists and surgeons, medical geneticists, genetic counselors, and allied healthcare professionals. Comprehensive evaluation and management of these patients includes collection of detailed phenotypic data to inform the broader community and identify new associated and causative genes of interest, genetic modifiers, and other risk factors. These programs optimize outcomes and reduce the overall burden in the population of acute aortic dissection and related comorbidities.

Mitral annular disjunction and mitral valve prolapse extrapolating adult data to an adolescent cohort?

PURPOSE OF REVIEW: The aim of this study is to provide an update on mitral valve prolapse (MVP) and mitral annular disjunction (MAD) and who may be at risk for ventricular arrhythmias and sudden cardiac death. RECENT FINDINGS: MVP is generally considered a benign condition. However, a small subset of patients may be at risk for life-threatening ventricular arrhythmias. Among the risk factors identified in adults include patients with bileaflet mitral valves, myxomatous changes, myocardial fibrosis, and the presence of MAD. Advances in multimodal imaging have allowed for improved identification of fibrosis, anatomical valve derangements, and the amount of MAD. Recent guidelines have suggested that patients with MVP with or without MAD may be at risk for life-threatening arrhythmias if they have had prior ventricular arrhythmias, ventricular dysfunction, or unexplained syncope. Yet, extrapolation of adult data to a pediatric cohort with similar MVP and MAD at this juncture is challenging. There is, however, early evidence that some pediatric patients with significant myocardial fibrosis or abnormal tissue Doppler may be at risk for ventricular tachycardia. SUMMARY: Mitral valve prolapse and mitral annular disjunction at times coexist and at other times can be seen as isolated entities. While the incidence of arrhythmic MVP is quite rare, there is increasing evidence that certain select adults with MVP may be at risk for ventricular tachycardia and sudden cardiac death. Future multicenter studies are needed to better understand the natural history of arrhythmic mitral valve disease and how early disease manifestation in children may impact findings now being reported in young adults.

Intracardiac tumor causing left-ventricular outflow-tract obstruction in a newborn.

The following report describes the case of newborn girl with an asymptomatic systolic murmur, which on imaging revealed a nearly obstructive mass in the left-ventricular outflow tract. The mass was resected and found to be consistent with a rhabdomyoma. Here, we describe the pathologic and clinical characteristics of this tumor.

Minimally invasive percutaneous pericardial ICD placement in an infant piglet model: Head-to-head comparison with an open surgical thoracotomy approach.

BACKGROUND: Epicardial implantable cardioverter-defibrillator (ICD) placement in infants, children, and patients with complex cardiac anatomy requires an open surgical thoracotomy and is associated with increased pain, longer length of stay, and higher cost. OBJECTIVE: The purpose of this study was to compare an open surgical epicardial placement approach with percutaneous pericardial placement of an ICD lead system in an infant piglet model. METHODS: Animals underwent either epicardial placement by direct suture fixation through a left thoracotomy or minimally invasive pericardial placement with thoracoscopic visualization. Initial lead testing and defibrillation threshold testing (DFT) were performed. After the 2-week survival period, repeat lead testing and DFT were performed before euthanasia. RESULTS: Minimally invasive placement was performed in 8 piglets and open surgical placement in 7 piglets without procedural morbidity or mortality. The mean initial DFT value was 10.5 J (range 3-28 J) in the minimally invasive group and 10.0 J (range 5-35 J) in the open surgical group (P = .90). After the survival period, the mean DFT value was 12.0 J (range 3-20 J) in the minimally invasive group and 12.3 J (range 3-35 J) in the open surgical group (P = .95). All lead and shock impedances, R-wave amplitudes, and ventricular pacing thresholds remained stable throughout the survival period. CONCLUSION: Compared with open surgical epicardial ICD lead placement, minimally invasive pericardial placement demonstrates an equivalent ability to effectively defibrillate the heart and has demonstrated similar lead stability. With continued technical development and operator experience, the minimally invasive method may provide a viable alternative to epicardial ICD lead placement in infants, children, and adults at risk of sudden cardiac death.

Implant and clinical characteristics for pediatric and congenital heart patients in the national cardiovascular data registry implantable cardioverter defibrillator registry.

BACKGROUND: In 2010, the National Cardiovascular Data Registry enhanced pediatric, nonatherosclerotic structural heart disease and congenital heart disease (CHD) data collection. This report characterizes CHD and pediatric patients undergoing implantable cardioverter defibrillator implantation. METHODS AND RESULTS: In this article, we report implantable cardioverter defibrillator procedures (April 2010 to December 2012) in the registry for 2 cohorts: (1) all patients with CHD (atrial septal defect, ventricular septal defect, tetralogy of Fallot, Ebstein anomaly, transposition of the great vessels, and common ventricle) and (2) patients <21 years. We evaluated indications and characteristics to include transvenous and nontransvenous lead implants, CHD type, and New York Heart Association class. There were 3139 CHD procedures, 1601 for patients <21 years and 126 for CHD <21 years. Implantable cardioverter defibrillator indications for patients with CHD were primary prevention in 1943 (61.9%) and secondary prevention in 1107 (35.2%). Pediatric patients had 935 (58.4%) primary prevention and 588 (36.7%) secondary prevention devices. Primary prevention had higher New York Heart Association class. Nontransvenous age (35.9 ± 23.2 versus 40.1 ± 24.6 years; P=0.05) and nontransvenous height (167.1 ± 18.9 cm; range, 53-193 cm versus 170.4 ± 13.1 cm; range, 61-203 cm; P<0.01) were lower than for transvenous patients. CHD and pediatrics had similar rates of transvenous (97%) and nontransvenous (3%) leads and did not differ from the overall registry. Transposition of the great vessels and common ventricle had higher rates of nontransvenous leads. CONCLUSIONS: Primary prevention exceeds secondary prevention for CHD and pediatrics. Nontransvenous lead patients were younger, with higher rates of transposition of the great vessels and common ventricle patients compared with transvenous lead patients.

Universal ECG changes in pediatric patients undergoing procainamide challenge.

BACKGROUND: Procainamide is known to prolong PR, QRS, and QTc intervals in adults and is utilized to unmask the distinct electrocardiographic signatures, including right bundle branch block pattern and right precordial ST segment elevation seen with Brugada syndrome. This study analyzes a pediatric case series of procainamide challenges done to evaluate for possible Brugada syndrome. Our goal was to quantify the impact of procainamide on electrocardiographic intervals in all pediatric patients, regardless of the eventual determination of Brugada syndrome status. METHODS: We retrospectively reviewed all children undergoing procainamide challenge, consecutively from March 2009 to September 2012. Patients received intravenous procainamide over 15 minutes. All electrocardiograms (ECGs) performed during the drug challenge were reviewed. Analysis and ECG measurements were performed by investigators blinded to clinical diagnoses. RESULTS: All patients undergoing procainamide infusion had prolongation of their PR (mean +14%; 0-45%), QRS (+13%; 2-49%), and QTc (+15%; 4-30%) intervals regardless of testing outcome. QTc prolongation to >460 ms following procainamide infusion occurred in 76% of patients. No sustained arrhythmias or adverse events occurred. CONCLUSIONS: ECG changes including prolongation of the PR, QRS, and QTc intervals were seen in all children who underwent procainamide challenge for evaluation of possible Brugada syndrome. An increase in the PR, QRS, and QTc intervals of at least 20% occurred in all children without any adverse events. The QTc prolongation was not completely explained by the QRS prolongation.

Minimally invasive resynchronization pacemaker: a pediatric animal model.

PURPOSE: We developed a minimally invasive epicardial pacemaker implantation method for infants and congenital heart disease patients for whom a transvenous approach is contraindicated. The piglet is an ideal model for technical development. DESCRIPTION: In 5 piglets we introduced a needle through subxiphoid approach under thoracoscopic guidance, inserting a wire into the pericardial space. Pacing leads were affixed to the left ventricular free wall and left atrial appendage. After verifying functionality with atrial and ventricular pacing and sensing, animals were euthanized. Pacemaker monitoring occurred daily for 4 days in the fifth animal. EVALUATION: Through minimally invasive pericardial access, we directly visualized and fixated pacing leads to the left ventricle and left atrial appendage, successfully pacing atrium and ventricle. Epicardial structures were visualized. One piglet had contralateral pneumothorax, which resolved with needle decompression. No other adverse events occurred. CONCLUSIONS: Minimally invasive epicardial pacemaker implantation in an infant model is feasible and effective. This innovation may be of value for pacing and resynchronization in infants and congenital heart disease patients. Survival studies with permanent generator implantation are under way.

The Pacific Asynchronous TeleHealth (PATH) system: review of 1,000 pediatric teleconsultations.

OBJECTIVE: The aim of this study was to evaluate the impact on pediatric care of the Pacific Asynchronous TeleHealth (PATH) system, a provider-to-provider teleconsultation platform utilized by military medical facilities throughout the Pacific Region. This review focuses on access to care, quality of care, and cost savings for the Department of Defense as a result of ongoing development of the PATH system from 2006 to 2009. METHODS: This is a retrospective review of 1,000 consecutive teleconsultations occurring from January 2006 to March 2009. Three pediatric subspecialists reviewed the characteristics of each teleconsultation and the ultimate outcome. RESULTS: The PATH system processed > 300 pediatric teleconsultations in 2009 from 20 hospitals and clinics throughout the Pacific Region. The number of teleconsultations has grown significantly since 2006. Median teleconsultation response time was 14.5 h with 97% of teleconsultations answered within 1 week. The majority (75%) of teleconsultations came from areas without host nation pediatric subspecialty resources. Most teleconsultations (72%) involved diagnostic questions, whereas 21% were primarily for treatment issues. Teleconsultations originated predominantly from outpatient clinics (90%), with question resolution in 60% of cases without a face-to-face subspecialty evaluation. Fifteen percent of teleconsultations resulted in patient transfer to our center for definitive diagnosis and treatment. The diagnostic and/or treatment plan was modified in 74% of teleconsultations. PATH precluded patient transfer in 12%-43% of teleconsultations (annual savings: $208,283-$746,348 per year) and generated an average of 1.7 relative value units per teleconsultation. CONCLUSIONS: PATH provided patient access to pediatric subspecialty expertise via provider-to-provider asynchronous teleconsultation. Internet-based pediatric subspecialty teleconsultation provides fast, convenient, cost-effective, quality pediatric care to populations of patients who might otherwise require transfer to a distant medical facility for more advanced care. PATH serves as a model for future asynchronous teleconsultation platforms in both the military and civilian healthcare arenas.